In clinical medicine, swelling of the brain occurs in several common disease states such as (1) traumatic brain injury, (2) stroke, (3) survivors of cardiac arrest, (4) meningitis, (5) encephalitis and (6) brain tumors. Other less common conditions can also produce swelling of the brain. Physicians currently use several methods to treat both the brain swelling and the elevated intracranial pressure associated with it. These methodologies include intracranial pressure monitoring, removal of cerebrospinal fluid if an intraventricular catheter is in place, mechanical ventilation to prevent hypoxia and hypercarbia, strict control of fluid balance to provide for a normal intravascular fluid volume while avoiding hypo-osmolality, use of osmolar agents to create a hyperosmolar state, elevating the head of the bed, sedation and paralysis as needed. Routine surveillance of the intracranial vault with CT scans of the head is also used to rule out space occupying lesions that would be amenable to surgical removal.
Recent studies have also shown that use of hypothermia with body temperatures lowered to 32-34 degrees Celsius within 4 hours of the onset of traumatic brain injury1 or cardiac arrest2 can improve neurological outcome.
In addition, uncontrolled hyperglycemia has been shown to adversely affect mortality rates in traumatic brain injury3, stroke4, and cardiac arrest5.
It has also been shown that strict control of blood glucose can improve mortality rates in post-operative patients and in medical ICU patients who remain in the ICU for at least three days.6,7,8,9 Unfortunately, these studies and others10 have shown that hypoglycaemia is a complication of strict glucose control utilizing an intravenous infusion of insulin.
In another treatment scenario, the continuous monitoring of serum osmolality, as provided by the catheter, will allow tighter control of serum osmolality, which may also improve neurological outcome in patients with cerebral edema.11 The iterative algorithm created to control an infusion of hypertonic saline will help clinicians achieve the goal of tight osmolality control.
Prior efforts in biomedical engineering have attempted to address similar goals. One of the earliest attempts at intravenous medical intervention is set forth in U.S. Pat. No. 4,072,146 (Howes 1978) entitled Venous Catheter Device. The Howes '146 patent discloses a catheter with a plurality of independent and non-communicating fluid conveying lumens housed within or formed in a single catheter. Each lumen transports a different fluid—or solution for entry into the patient's bloodstream.
U.S. Pat. No. 4,403,984 (Ash 1983) expands upon the concept of intravenous infusion and discloses a catheter with sensors for measuring in vivo the physical properties of blood. The signals from the sensor control infusion of medication, such as insulin, in response to a glucose measurement. The Ash '984 catheter measures osmolality via electrolytic conductivity of the blood. In one embodiment, Ash uses the osmolality reference signal as the insulin distribution control signal.
A series of patents issued to Schulman and granted as U.S. Pat. Nos. 5,497,772; 5,531,679; 5,660,163 show glucose sensors positioned within a patient's bloodstream for glucose and oxygen monitoring purposes. Schulman, however, does not show any in-depth means of adjusting glucose in a controlled process.
In determining blood conductivity, noted as useful in the Ash '984 patent above, U.S. Pat. No. 5,827,192 (Gopakumaran 1998) discloses an in vivo method of determining blood conductivity within the patient's heart. By utilizing spaced electrodes on a catheter, the Gopakumaran patent shows that blood conductivity can be determined from an induced voltage from a known current.
Still, however, none of the patents discussed above utilize a truly closed loop process for measuring multiple parameters, such as conductivity, osmolality, and glucose concentration, to adjust blood chemistry via infusions of multiple medicines or fluids. In regard to the osmolality measurements described herein, a conductivity sensor such as that of U.S. Pat. No. 4,380,237 (Newbower 1983) is available to provide blood conductivity measurements. Newbower, however, is limited in its disclosure to cardiac measurements that do not focus on glucose or osmolality readings. The Newbower '237 patent, then is limited in its disclosure.
The only known patent that even broaches the topic of a multi-variable closed loop system is U.S. Pat. No. 6,740,072 (Starkweather 2004). The Starkweather '072 patent discloses a system and method of providing closed loop infusion delivery systems that determine the volume of an infused substance via a sensed biological parameter. The Starkweather '072 controller is a multiple input single output controller using a proportional component and a derivative component of blood glucose measurements. The proportional component is simply the difference between the measured glucose level and the desired set point. The derivative component shows the rate of change for real time glucose level measurements. An appropriate controller then adjusts the single output—insulin dose. Starkweather, however, is limited in its ability to account for nonlinear physiological responses such as blood levels for glucose and osmolality. Specifically, in hypoglycaemic states the Starkweather controller's only response is to lower or stop the insulin infusion. It does not include any active interventions to raise the blood glucose level such as initiation of a glucagon infusion in the outpatient setting, or initiation of a glucagon or dextrose infusion in the inpatient setting.
Even in light of the above noted developments, there continues to be a need, in the art of blood chemistry intervention for a means of monitoring and controlling non-linear physiological responses in the blood stream. In particular, there is a need for a closed loop system that successfully adjusts blood chemistry parameters, including but not limited to glucose and osmolality, in real time emergency and non-emergency settings.
To accomplish these and other goals of the invention, the apparatus and system disclosed herein provide a means for closed loop electronic monitoring and blood chemistry regulation.